Findings from a new study of 141 adults add to an ongoing medical debate over which patients with symptoms of celiac disease should go on a gluten-free diet. Published in ACS' Journal of Proteome Research, the study concludes that people currently diagnosed as “potential” celiac disease patients and not advised to follow a gluten-free diet may not be “potential” patients at all. Rather, the scientists found that these patients have the same distinctive metabolic fingerprint as patients with full-blown disease who do benefit from gluten-free diets.

In the study, Ivano Bertini and colleagues explain that celiac disease is an autoimmune digestive disorder characterized by the inability to digest a protein called gliadin, a component of gluten, which is found in wheat, rye, and barley. The condition causes diarrhea, bloating, and other symptoms in over 3 million people in the United States alone. Treatment is avoidance of foods containing gluten. But the disease is often undiagnosed or misdiagnosed. Definitive diagnosis involves biopsy of the small intestine, showing tissue damage. People with a positive blood test for the condition but no positive biopsy usually are diagnosed as “potential” celiac patients and may or may not be advised to follow a gluten-free diet.

The scientists used magnetic resonance metabolic profiling to analyze the biochemical markers in the blood and urine of 61 patients with celiac disease, 29 with potential celiac disease, and 51 healthy people. They found that those with potential disease largely shared the same profile as those with the confirmed disease and that the biochemical markers in both groups differed significantly from those of the healthy individuals. “Our results demonstrate that metabolic alterations may precede the development of small intestinal villous atrophy and provide a further rationale for early institution of gluten-free diet in patients with potential celiac disease, as recently suggested by prospective clinical studies,” the scientists conclude.

People with celiac disease may develop osteoporosis due to immune-system attacks on bone tissue (N Engl J Med. 2009; 361:1459-1465). Although osteoporosis is a known complication of celiac disease, scientists have always believed that it occurred because celiac patients cannot properly absorb calcium and vitamin D from their diet and were therefore unable to maintain healthy bone tissue.

At the heart of this development is the protein osteoprotegerin, which plays a crucial role in maintaining bone health by controlling the rate at which bone tissue is removed. Researchers from the United Kingdom's University of Edinburgh and University of Liverpool detected autoantibodies against osteoprotegerin in several patients with celiac disease.

“Such autoantibodies may be associated with the development of high-turnover osteoporosis, but whether autoantibodies against osteoprotegerin commonly contribute to the pathogenesis of osteoporosis in patients with celiac disease remains to be determined,” the investigators conclude.

Thompson and her colleagues analyzed 22 naturally gluten-free grains, seeds, and flours off supermarket shelves, only looking at products that weren't specifically advertised as being gluten-free. They tested the amount of gluten in those products against a proposed Food and Drug Administration limit for any product labeled gluten-free, 20 parts contaminant per million parts product.

Seven of the 22 products wouldn't pass the FDA's gluten-free test – and one product, a type of soy flour, had a gluten content of almost 3,000 parts per million, the authors found. Other products from the sample that weren't truly gluten-free included millet flour and grain, buckwheat flour, and sorghum flour.

The study was too small to give consumers a good idea of how common it is for these products to be contaminated or what products should make people with celiac disease especially wary, Thompson said.

But “it is a red flag,” Cynthia Kupper, the executive director of the Gluten Intolerance Group of North America, who was not involved with the research, told Reuters Health.

Even companies that do explicitly label their products as gluten-free, she said, might not always test products they assume won't contain any gluten. The study “is a wake-up call to the food industry,” said Kupper. Companies “need to make sure (their products) are truly gluten-free.”

Without an FDA regulation in place, there is still no hard-and-fast government definition of what gluten-free means, Thompson said.

That makes it harder to keep companies that might skimp on their testing accountable.

“It's hoped but certainly not assumed that manufacturers who are putting the (gluten-free) label on their single-ingredient grains and flours are testing their ingredients,” Thompson said. “Do all manufacturers test? Probably not.”

Under the proposed gluten-free labeling rule, the FDA could conduct inspections of manufacturers that claim their products are gluten-free and analyze those products.

Thompson and Kupper agreed that more research needs to be done to find out the scope of the contamination problem. In the meantime, Thompson said, people with celiac disease are probably better off purchasing grains, seeds, and flours with the gluten-free label. The products can't be guaranteed to be completely free of gluten, but it is more likely that they will have been tested, she said.

The team set out to examine levels of depression and anxiety between adults with celiac disease following a gluten-free diet and in control subjects drawn from the general population.

For their study, the team used the Hospital Anxiety and Depression Scale to measure levels of anxiety, depression, and likely anxiety or depressive disorder, in 441 adult patients with celiac disease recruited by the German Celiac Society. They then conducted the same assessments on 235 comparable patients with inflammatory bowel disease (IBD), either in remission or with slight disease activity. They did the same for the cross-sample control group of 441 adults from the general population.

The team used regression analysis to test possible demographic and disease-related predictors of anxiety and depression in celiac disease. Demographic predictors included age, sex, social class, and family status. Disease-related predictors included Latency to diagnosis, duration of GFD, compliance with GFD, thyroid disease.

The team found that female gender (P = 0.01) was the main predictor (R(2) = 0.07) of anxiety levels in patients with celiac disease. Female patients had a higher risk for a probable anxiety disorder (OR = 3.6, 95% CI: 1.3-9.4, P = 0.01) Patients who lived alone (OR = 0.5, 95% CI: 0.2-0.9, P = 0.05) enjoyed a lower risk of anxiety disorder. None of the demographic and medical variables for which the team screened predicted either depression levels or risk for a probable depressive disorders.

Patients with celiac disease showed anxiety levels of 6.6 +/- 3.4, and those with IBD, anxiety levels of 6.9 +/- 3.7, both higher than the general population's level of 4.6 +/- 3.3 – (both P < 0.001). Depression levels were similar for people with celiac disease (4.2 +/- 3.4), IBD (4.6 +/- 3.4) and the general population (4.2 +/- 3.8) (P = 0.3). Rates of likely anxiety disorders in people with celiac disease were 16.8%, and 14.0% for IBD, both higher than the rates of 5.7% in the general population (P < 0.001). All three groups showed similar rates of probable depressive disorder (P = 0.1).

Their results provide strong indications that adult women with celiac disease on a gluten-free diet suffer higher rates of anxiety than persons of the general population. They encourage clinicians to provide anxiety screens for adult women with celiac disease on a gluten-free diet.

Patients who use vitamin supplements also showed lower levels of plasma homocysteine than in patients who did not (P = 0.001) or healthy controls (P = 0.003). Vitamin B6 and folate were both associated with homocysteine levels, whereas vitamin B12 was not. Twenty-four (48%) of 50 controls and 23 (50%) of 46 of the celiac disease patients carried the MTHFR thermolabile variant T-allele (P = 0.89).

The research team concludes that Homocysteine levels are dependent on Marsh classification and the regular use of B-vitamin supplements reduces of homocysteine levels in patients with celiac disease.The study confirms earlier studies suggesting that both the presence and severity of celiac disease determined homocysteine levels.

The regular use of supplemental B vitamins resulted in higher levels of serum vitamin B6, folate, vitamin B12 and lower levels of plasma homocysteine in patients with celiac disease. Moreover, supplemental B vitamins seem to offer protection against the effects of villous atrophy on homocysteine levels, independent of the genetic susceptibility status as determined by carriage of the C677T polymorphism of 5,10 methylenetetrahydrofolate reductase.

Researchers aren't sure why there could be a link between the mode of delivery and celiac disease, but one possible explanation is that children born via C-section don't pick up the same microbes from their mothers as babies that pass through the vaginal canal, Hornef said. This alters the infant's colonization with gut microflora, or “good” microbes, that aid in digestion and fending off pathogens.

Previous research suggests there are differences in the intestinal bacterial flora between children born vaginally or by C-section.

“We are only beginning to understand the complexity of the host-microbial interaction at the intestinal mucosa, and it is difficult to make firm conclusions at this stage,” Hornef said.

Does any of this suggest that women with a personal or family history of celiac disease avoid C-sections? According to both Green and Hornef, it's too early to make firm recommendations.

“I think our data are not evidence enough to already make a medical recommendation, but rather they shed light on a possibly ill-studied issue,” Hornef said. “The data first need to be confirmed.”